Rubinstein-Taybi syndrome ... (Rubinstein-Taybi syndrome) - Genes CREBBP and EP300.  

The Rubinstein-Taybi syndrome is a disorder characterized by short stature, moderate to profound intellectual disability, characteristic and thumbs and first toes feet wide facial features. Additional features of the disease may include ocular abnormalities, cardiac and renal defects, dental problems, and obesity. These signs and symptoms vary among affected individuals. People with this condition have a higher risk of developing cancer and noncancerous tumors, including certain types of brain tumors. Leukemia occurs most often in people with Rubinstein-Taybi syndrome. Rarely, the Rubinstein-Taybi syndrome may involve serious complications such as a lack of weight gain, growth retardation and life threatening infections. Newborns born with this severe form of the disease survive, usually only during early childhood.

This process is due to mutations in genes CREBBP and EP300. Mutations in the gene CREBBP, located on the short arm (p) of chromosome 16 (16p13.3) are responsible for some cases of the syndrome. This gene encodes a protein that helps control the activity of many other genes. This CREB binding protein, plays an important role in regulating cell growth and division and is essential for normal fetal development. If a copy of the mutated gene CREBBP is removed, the cells produce only half the normal amount of CREB binding protein. Although a reduction in the amount of this protein alters the normal development before and after birth, it has not been determined how generate specific signs and symptoms of Rubinstein-Taybi syndrome.

They have identified more than 90 mutations in the gene CREBBP causing the syndrome, including deletions and insertions of genetic material into the gene and changes the indiviruales in DNA nucleotides. Genetic changes that affect CREBBP gene have been associated with certain types of neoplasias such as acute myeloid leukemia (AML), chronic myelogenous leukemia or ovarian cancer.

Mutations in the gene EP300, located on the long (q) arm of chromosome 22 (22q13.2), cause a small percentage of cases of the syndrome. This gene encodes the p300 protein. This protein controls the activity of many genes in tissues throughout the body, playing an essential role in controlling cell growth and division. The p300 protein appears to be critical for normal development before and after birth. The p300 protein performs its function by activating the transcription of genes. Specifically, p300 transcription factors connected with the protein complex holding transcription. On the basis of this function is a transcriptional coactivator p300.

They have identified several mutations in the gene that cause EP300 Rubinstein-Taybi syndrome. Mutations in the gene EP300 inactivate a copy of the gene in every cell, which interferes with normal development causing the typical characteristics of the syndrome. Signs and symptoms of mutations in the gene EP300 are similar to those with mutations in the gene CREBBP. However, it has been suggested that mutations in the EP300 gene may be associated with milder skeletal changes in the hands and feet.

About half of people with Rubinstein-Taybi syndrome have identified a mutation in the gene CREBBP or EP300. In these cases, the cause of the disease is unknown, so other genes might be involved.

This syndrome is considered to have an autosomal dominant inheritance, which means that a copy of the altered gene in each cell is sufficient to cause disease. Most cases result from new mutations in the gene and occur in people with no history of disease in your family.  

Tests in IVAMI: in IVAMI perform detection of mutations associated with Rubinstein-Taybi syndrome, by complete PCR amplification of exons and EP300 CREBBP respectively gene and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).